liu.seSök publikationer i DiVA
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
The Expression of Psoriasin (S100A7) and CD24 Is Linked and Related to the Differentiation of Mammary Epithelial Cells
Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
Sahlgrens University Hospital, Sweden .
Harvard University, USA .
Visa övriga samt affilieringar
2012 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 12Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyperproliferative skin disorder psoriasis. The gene that encodes psoriasin and many other S100 genes are located within a gene cluster on chromosome region 1q21, known as the epidermal differentiation complex. This cluster contains genes for several differentiation markers that play important roles in the terminal differentiation of the epidermis. The purpose of the present study was to evaluate the role of psoriasin in the differentiation process of mammary epithelial cells. Normal mammary epithelial cells (MCF10A) cultured in confluence and suspension, conditions known to induce psoriasin expression, demonstrated a shift towards a more differentiated phenotype indicated by an increase in the expression of the luminal differentiation markers CD24 and MUC1 and the reduced expression of the breast stem cell marker CD44. The expression of psoriasin and MUC1 was most pronounced in the CD24(+)-enriched fraction of confluent MCF10A cells. The shift towards a more differentiated phenotype was abolished upon the downregulation of psoriasin using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Using specific inhibitors, we showed that psoriasin and CD24 expression was regulated by reactive oxygen species (ROS) and the nuclear factor (NF)-kappa B signaling pathways. While immunohistochemical analyses of DCIS showed heterogeneity, the expression of psoriasin and CD24 showed a similar staining pattern. Our findings suggest that the expression of psoriasin is linked to the luminal differentiation marker CD24 in mammary epithelial cells. Psoriasin demonstrated an essential role in the shift towards a more differentiated CD24(+) phenotype, supporting the hypothesis that psoriasin plays a role in the differentiation of luminal mammary epithelial cells.

Ort, förlag, år, upplaga, sidor
Public Library of Science , 2012. Vol. 7, nr 12
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-88366DOI: 10.1371/journal.pone.0053119ISI: 000312829100122OAI: oai:DiVA.org:liu-88366DiVA, id: diva2:602877
Anmärkning

Funding Agencies|Ingrid Asp Foundation||Swedish Cancer Society||Swedish Psoriasis Association||Welander Foundation||

Tillgänglig från: 2013-02-04 Skapad: 2013-02-04 Senast uppdaterad: 2017-12-06
Ingår i avhandling
1. Psoriasin For Better or for Worse in Sickness and in Health: The Role of Psoriasin in Angiogenesis and Differentation of Epithelial Cells
Öppna denna publikation i ny flik eller fönster >>Psoriasin For Better or for Worse in Sickness and in Health: The Role of Psoriasin in Angiogenesis and Differentation of Epithelial Cells
2014 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyper-proliferative skin disorder psoriasis. Both breast cancer and psoriasis are diseases which are characterized by hyperproliferation and a disturbed differentiation of the epithelial cells as well as a pronounced angiogenesis. The potential role of psoriasin in angiogenesis and the epithelial differentiation remain unclear.

The aim of this thesis was to investigate the cellular effects of psoriasin in angiogenesis and the differentiation processes, with special emphasis on breast cancer and psoriasis.

We found that psoriasin expression was induced in mammary epithelial cells and keratinocytes by oxidative stress. Psoriasin expression was shown to induce vascular endothelial growth factor (VEGF) expression and several other pro-angiogenic factors in epithelial cells. Upon down-regulation of psoriasin, H2O2-induced expression of VEGF was decreased as well as the pro-angiogenic factors heparin-binding EGF-like growth factor (HBEGF) and matrix metalloproteinase (MMP)-1. Extracellular psoriasin contributed to the subsequent induction of proliferation, migration and tube formation of endothelial cells. The proliferative effect of psoriasin was shown to be mediated by the receptor for advanced glycation end products (RAGE). Furthermore, psoriasin induced reactive oxygen species (ROS) in both endothelial and epithelial cells through the action of RAGE, and contributed to the expression of the pro-angiogenic factors in endothelial cells.

The expression of psoriasin was up-regulated in mammary epithelial cells and keratinocytes in response to differentiation-inducing stimuli and was shown to be regulated by pathways involved in epithelial cell differentiation. Upon psoriasin down-regulation the shift towards a more differentiated CD24+-phenotype of mammary epithelial cells was abolished. Furthermore, the expression of the differentiation markers involucrin, desmoglein 1, transglutaminase 1 and CD24 was decreased in keratinocytes upon down-regulation of psoriasin expression. In vivo we demonstrated a gradient of psoriasin expression in the psoriatic epidermis, with intense expression in the suprabasal differentiated layers, and a similar staining pattern between psoriasin and the differentiation marker CD24 in DCIS tumors.

In conclusion, our findings describe psoriasin as a mediator in the angiogenic process and a contributor of epithelial cell differentiation. Consequently, psoriasin is possibly a contributor to the development and progression of breast cancer and psoriasis and a potential target in the treatment of these diseases.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2014. s. 58
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1412
Nationell ämneskategori
Dermatologi och venereologi Medicinska och farmaceutiska grundvetenskaper
Identifikatorer
urn:nbn:se:liu:diva-110031 (URN)10.3384/diss.diva-110031 (DOI)978-91-7519-283-3 (ISBN)
Disputation
2014-09-26, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2014-09-01 Skapad: 2014-09-01 Senast uppdaterad: 2019-11-19Bibliografiskt granskad

Open Access i DiVA

fulltext(958 kB)377 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 958 kBChecksumma SHA-512
3ddda1b40db0b3b54753dcd7671b81002e0228c582154e751be2e1797710d08bb135574505e6d4cdfbd2a78220aff5aeea399fb29c630450d1b5ce79b1566873
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltext

Personposter BETA

Petersson, StinaEnerbäck, Charlotta

Sök vidare i DiVA

Av författaren/redaktören
Petersson, StinaEnerbäck, Charlotta
Av organisationen
Institutionen för klinisk och experimentell medicinHälsouniversitetetHudkliniken i ÖstergötlandCellbiologi
I samma tidskrift
PLoS ONE
Medicin och hälsovetenskap

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 377 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 125 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf